PROJECT SUMMARY/ABSTRACT The overarching strategy of the University of Pittsburgh (Pitt) clinical research site (CRS) together with our collaborative clinical site at The Ohio State University (OSU) of the Multicenter AIDS Cohort Study (MACS)/Woman?s Interagency HIV Study (WIHS) Combined Cohort Study (MACS/WIHS CCS) is to support, complement and accelerate the CCS unified scientific agenda (USA) by leveraging the strengths and scientific expertise of CRS investigators. We propose to continue to expand on our 35 years of extensive research on the natural history of HIV infection. The central hypothesis of this grant application is that, as men and women with chronic HIV infection age, they increase their risks for serious, life-shortening comorbidities beyond those of comparable age, uninfected persons, and this could differ between men and women. As directed by NIH RFA- HL-19-008, the CRS will provide robust and inclusive leadership focused on five specific aims of the USA, and targeted collaborative support for the five other aims, to improve our understanding of the epidemiologic, clinical, virologic, immunologic, and behavioral relationships of HIV infection to chronic comorbidities in men and women that represent the current HIV epidemic in the United States. The CRS will also contribute longitudinal data and biological specimens for collaborative research projects on HIV led by CCS and non-CCS investigators. This research is important to fulfill our mission of improving clinical management, increasing survival and controlling, preventing and curing HIV infection. The CRS will provide the most current and innovative epidemiological, clinical and laboratory methods and psychosocial research protocols to accomplish our 5 leadership specific aims. The Pitt/OSU CRS will be led by a triumvirate of MPIs and several CoIs with broad expertise needed to lead five highly specialized CCS USA Specific Aims (Aim 2: Pulmonary/Sleep [Morris]; Aim 3: Neurocognitive [Becker]; Aim 6: HIV/Pathogenesis [Macatangay]; Aim 7: Psychosocial [Stall]; Aim 9: Platform [Rinaldo, Kingsley]) and to provide insight for the 5 other Specific Aims (Aim 1: Cardiovascular [Kingsley, Martinson], Aim 4: Aging [Koletar], Aim 5: Cancer [Jenkins], Aim 8: Health Disparities [Krier], Aim 10: Career Development [Sluis- Cremer]. With this plan the Pitt/OSU CRS addresses the basic justification of the FOA, i.e., that the impact of HIV, its treatment, and the legacy of immune suppression need to be more fully understood to optimize the health of people living with HIV.